Adrenal insufficiency is caused by the underproduction of adrenocortical hormones.
Definition of terms
| Term | Definition |
|---|---|
| Primary adrenal insufficiency (Addison’s disease) | This is primary adrenal insufficiency. Although rare, it can be fatal since destruction of the adrenal cortex leads to glucocorticoid and mineralocorticoid deficiency. Addison’s disease is associated with hyperpigmentation. The most common cause is autoimmune adrenalitis. |
| Secondary adrenal insufficiency | This is the most common cause of adrenal insufficiency. It is caused by inadequate adrenocorticotropic hormone (ACTH) production due to loss or damage to the pituitary gland. |
| Tertiary adrenal insufficiency | This is caused by inadequate corticotropin-releasing hormone (CRH) from the hypothalamus, commonly from abrupt withdrawal of chronic corticosteroid production. |
- Causes of adrenal insufficiency
- Autoimmune adrenalitis (70 – 90%)
- Infection
- Tuberculosis
- Fungal infections
- HIV
- CMV
- Genetic disorders
- Congenitla adrenal hyperplasia (CYP21A2)
- AIRE (APS-1)
- Metastatic infiltration
- Sheehan’s syndrome
- Adrenal hemorrhage
- Trauma
- Anticoagulation
- Sepsis
- Medications
- Prolonged use of glucocorticoids
- Prolonged ketoconazole
- Pathophysiology
- Cortisol deficiency → hypoglycaemia, increased susceptibility to infection, and inadequate response to stressors
- Aldosterone deficiency → hyponatremia, hyperkalaemia, hypotension, and impaired renal function
- Dehydroepiandrosterone (DHEA) and androstenedione deficiency → reduced body hair and decreased libido
- Reduced adrenal cortex function → increased ACTH production and melanocyte-stimulating hormone (MSH) production → hyperpigmentation
- Signs and symptoms
- Orthostatic hypotension
- Lethargy
- Weakness
- Anorexia
- Abdominal pain
- Nausea and vomiting
- Weight loss
- Salt-craving
- Hyperpigmentation in Addison’s disease
- Especially of the palmar creases and buccal mucosa
- Vitiligo
- Loss of pubic hair in women
- Differentials
- Adrenal tuberculosis
- Sepsis
- Investigations
- Hypoglycaemia
- Hyponatremia
- Hyperkalaemia
- Raised urea and creatinine due to dehydration
- Hypercalcemia
- 9 am serum cortisol: often falsely normal
- 100 – 500 nmol/L requires an ACTH stimulation test
- < 100 nmol/L is abnormal
- Short ACTH (Synacthen) stimulation test to confirm the diagnosis
- No change or insufficient cortisol production in response to ACTH stimulation in Addison’s disease or significant adrenal atrophy due to prolonged secondary adrenal insufficiency
- Increased cortisol in secondary adrenal insufficiency
- 9 am ACTH level to differentiate primary from secondary causes
- Inappropriately high in primary causes (Addison’s disease)
- Low in secondary causes
- CT or MRI of the adrenal glands and pituitary if structural pathology is suspected
- Abdominal and Chest radiographs for past tuberculosis (upper zone fibrosis) or adrenal calcification
- Adrenal autoantibodies for autoimmune adrenalitis (21-hydroxylase autoantibodies)
- Further testing for tuberculosis, histoplasma, or metastatic diseases
- Treatment
- Medical alert bracelet declaring steroid use
- Hydrocortisone for glucocorticoid replacement
- Given in the morning
- Double dose in case of intercurrent illness
- Fludrocortisone for mineralocorticoid replacement
- Secondary adrenal insufficiency may not require mineralocorticoid replacement
- Follow-up yearly
- Monitor for autoimmune disease, e.g., pernicious anaemia
- Complications
- Adrenal crisis
- Osteoporosis due to long-term glucocorticoid therapy
- Infection